Genetic Variant NM_000102.4:c.1243+83C>A (chr10-102831425-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000102.4(CYP17A1):c.1243+83C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,579,362 control chromosomes in the GnomAD database, including 31,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2513 hom., cov: 31)

Exomes 𝑓: 0.20 ( 28715 hom. )

Consequence

CYP17A1
NM_000102.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.158

Variant links:

Genes affected

CYP17A1 (HGNC:2593): (cytochrome P450 family 17 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. It has both 17alpha-hydroxylase and 17,20-lyase activities and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. Mutations in this gene are associated with isolated steroid-17 alpha-hydroxylase deficiency, 17-alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia. [provided by RefSeq, Jul 2008]

CYP17A1 links:

WBP1L (HGNC:23510): (WW domain binding protein 1 like) Predicted to enable ubiquitin protein ligase binding activity. Predicted to act upstream of or within CXCL12-activated CXCR4 signaling pathway; hemopoiesis; and positive regulation of protein ubiquitination. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

WBP1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 10-102831425-G-T is Benign according to our data. Variant chr10-102831425-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1177608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP17A1	NM_000102.4 link	c.1243+83C>A		intron_variant	Intron 7 of 7	ENST00000369887.4	NP_000093.1	P05093Q1HB44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP17A1	ENST00000369887.4 link	c.1243+83C>A		intron_variant	Intron 7 of 7	1	NM_000102.4	ENSP00000358903.3		P05093

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24425

AN:

151968

Hom.:

2506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0425

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.159

GnomAD4 exome

AF:

0.196

AC:

279263

AN:

1427276

Hom.:

28715

AF XY:

0.196

AC XY:

139026

AN XY:

707716

show subpopulations

Gnomad4 AFR exome

AF:

0.0340

Gnomad4 AMR exome

AF:

0.290

Gnomad4 ASJ exome

AF:

0.167

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.293

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.161

AC:

24434

AN:

152086

Hom.:

2513

Cov.:

AF XY:

0.168

AC XY:

12461

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0424

Gnomad4 AMR

AF:

0.235

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.191

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.175

Hom.:

390

Bravo

AF:

0.151

Asia WGS

AF:

0.196

AC:

680

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Deficiency of steroid 17-alpha-monooxygenase

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.9

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over